ALTERATION OF THE CHEMOTACTIC RESPONSE OF HUMAN SKIN FIBROBLASTS TO PDGF BY GROWTH-FACTORS

Platelet-derived growth factor (PDGF) is a potent mitogen and chemoatt ractant for fibroblastic cells. In the early stage of wound healing, P DGF is released from aggregated platelets and it is believed that its chemotactic activity may play a key role in the influx of connective t issue cells into wound sites. Using the Boyden chamber assay, we inves tigated factors that alter the migratory response of human skin fibrob lasts to PDGF. The response was related to the growth state of cells; that is, growing cells at low cell density exhibited a greater migrato ry response to PDGF than density-arrested quiescent cells. The level o f random migration was also elevated in growing cells, compared to qui escent cells. The chemotactic response after 3-h exposure to serum was markedly decreased (>50%). Three-hour preincubation of the cells with transforming growth factor-beta (TGF-beta) or with epidermal growth f actor reduced the migratory response to approximately half that in the nonstimulated control. In contrast, cells treated with TGF-beta or ba sic fibroblast growth factor for 24 h exhibited a two- to threefold gr eater chemotactic response to PDGF than control cells. This stimulator y effect of TGF-beta on the fibroblast migration induced by PDGF sugge sts that TGF-beta acts synergistically with PDGF on the influx of conn ective tissue cells into human wound sites and may explain the potent wound healing activity of TGF-beta in vivo. (C) 1994 Academic Press, I nc.